Risk of cancer with immunosuppressants compared to immunomodulators in multiple sclerosis: A nested case-control study within the French nationwide claims database

Purpose: The objective was to compare the risk of malignancies in real-world settings between exclusive immunosuppressant (IS) and immunomodulator (IM) use in multiple sclerosis (MS).Methods: A nested case-control study was designed within a new-user cohort of all patients with MS who initiated a first IM or IS between 2008 and 2014, and without cancer history, using the information of the SNDS nationwide French claims data-base. Incident cancer cases were matched with up to six controls on year of birth, sex, initiation date, and disease risk score of cancer. A conditional logistic regression (odds ratio [95% confidence interval]) was used to compare exclusive IS versus IM use during follow-up and according to three use durations.Results: From 28 720 newly treated patients with MS, 407 incident cancers were observed during the follow-up with 2324 matched controls. A significant increase in cancer risk was observed for IS compared with IM (1.36 [1.05, 1.77]), with similar increases for the first 2 years of use but not for =2 years (1.06 [0.65, 1.75]). Similar increase was also observed for IS with indications other than MS (1.37 [1.04, 1.81]) but not for IS indicated only in MS (1.03 [0.45, 2.34]).Conclusions: Compared with IM, a 37% increase in cancer risk was observed for IS with indications other than MS and used for a short duration (=2 years) but not for IS indicated only in MS. The absence of risk for prolonged exposure of IS with indica-tions other than MS is not in favor of a causal relation with these drugs.